The purpose of the proposed work summarized in this communication examine the effects of methadone on behavior; and how certain biological factors (genetic background and neurotransmitter systems) and environmental factors (novelty and schedule of reinforcing stimuli) influence the behavioral response to the drug. Studies are proposed, using inbred strains of mice which have opposite changes in activity following injections of methadone, which will allow us to determine if the genetic influence on drug reaction generalizes to drug effects in other behavioral situations and if the genetic difference in drug reaction is mediated by differences in neural systems utilizing monoamines as neurotransmitters. These studies will also allow a direct comparison of drug induced behavioral and neurochemical effects by controlling dose and time of drug injection. Other studies are proposed which will allow us to determine the influence of environmental novelty on drug reaction and the influence of the schedule on which reinforcing stimuli are delivered on drug induced behavioral changes. Finally, studies are proposed to determine the influence of prenatal exposure to methadone on subsequent behavioral reaction to the drug after maturity.